Fig. 1.

a Genetic associations with schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. Odds ratios (y-axis, −log10, transformed to be > 1) and minor allele frequencies (MAF, x-axis, −log10, transformed to be ≤ 0.5) for single-nucleotide polymorphisms (SNPs), rare coding variants (RCVs), and rare copy number variants (CNVs), which were derived from the studies outlined in Table 2. We note that for ASD, as odds ratios have not been estimated for all classes of mutation, we have plotted the smoothed relative risk for RCVs (as reported in [14]) and odds ratios for CNVs and SNPs on the same scale, labeled as “Effect sizes,” for illustrative purposes. There is a general trend for a negative correlation between odds ratio and MAF, which reflects the degree to which selection removes risk alleles from the population. b Polygenic liability threshold model. For polygenic neuropsychiatric disorders, diverse classes of mutation contribute to liability, with additive models currently providing the best fit to the data [26]